| 1. |
|
|
| 2. |
|
|
| 3. |
- Berntsen, S., et al.
(författare)
-
A systematic review and meta-analysis on the association between ICSI and chromosome abnormalities
- 2021
-
Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 27:5, s. 801-847
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural abnormalities, as well as inherited abnormalities was described in children conceived by ICSI compared to both naturally conceived (NC) children and children conceived by standard IVF. The explanation for the observed increase in prevalence is not clear and has been suggested to reflect parental factors (e.g. age or sperm quality) or to be a result of the ICSI procedure itself. Over the years, the procedure, as well as the patient group, and indications for ICSI treatment have changed. OBJECTIVE AND RATIONALE: The objective of this systematic review and meta-analysis was to assess the prevalence of chromosome abnormalities in ICSI pregnancies and children and to examine any potentially increased risk compared to standard IVF and NC. SEARCH METHODS: Pubmed, Embase, Cochrane Libraries and Web of Science up to October 2020 were searched. Primary outcome measures were overall chromosome abnormalities and de novo abnormalities (including sex chromosome abnormalities and autosomal abnormalities). The secondary outcome was inherited abnormalities. We followed the PRISMA guidelines and relevant meta-analyses were performed. OUTCOMES: The search included 4648 articles, out of which 27 met the inclusion criteria, and 19 were included in quantitative synthesis (meta-analyses). The prevalence of chromosome abnormalities varied considerably between studies, possibly explained by large differences in sample size and patient demographics. Only five studies were eligible for pooled analyses on adjusted data. All studies had a critical risk of bias. Results from pooled adjusted data showed no evidence of an increased risk of overall chromosome abnormalities when comparing ICSI to either standard IVF (aOR 0.75 (95% CI 0.41-1.38)) or NC (aOR 1.29 (95% CI 0.69-2.43)). In contrast, meta-analyses on unadjusted data showed an increased risk of overall chromosome abnormalities in ICSI compared to both standard IVF (OR 1.42 (95% CI 1.09-1.85)) and NC (OR 2.46 (95% CI 1.52-3.99)) and an increased risk of de novo abnormalities in ICSI compared to NC (OR 2.62 (95% CI 2.07-3.31)). Yet, based on a very low certainty of evidence, the conclusion remains, that no indication of an increased risk of chromosome abnormalities in ICSI offspring could be found. If an increased risk of chromosome abnormalities in selected ICSI offspring should exist, the absolute risk continues to be small. WIDER IMPLICATIONS: This review provides an extensive overview of the existing evidence on the relationship between ICSI and chromosome abnormalities in the offspring. We highlight the need for well-designed large, prospective, controlled studies with systematic cytogenetic testing. Existing data are limited and, in many cases, marred by critical levels of bias.
|
|
| 4. |
- Henningsen, A. A., et al.
(författare)
-
Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group
- 2020
-
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:5, s. 1178-1184
-
Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is the risk of imprinting disorders increased in children conceived after ART? SUMMARY ANSWER: We found an adjusted odds ratio (AOR) of 2.84 [95% CI: 1.34-6.01] for Beckwith-Wiedemann syndrome in ART children, while the risk of Prader-Willi syndrome, Silver-Russell syndrome or Angelman syndrome was not increased in children conceived after ART. WHAT IS KNOWN ALREADY: Earlier studies, most of them small, have suggested an association between ART and imprinting disorders. STUDY DESIGN, SIZE, DURATION: This was a binational register-based cohort study. All children conceived by ART in Denmark (n = 45 393, born between 1994 and 2014) and in Finland (n = 29 244, born between 1990 and 2014) were identified. The full background populations born during the same time periods in the two countries were included as controls. Odds ratios of imprinting disorders in ART children compared with naturally conceived (NC) children were calculated. The median follow-up time was 8 years and 9 months for ART children and 11 years and 9 months for NC children. PARTICIPANTS/MATERIALS, SETTING, METHODS: From the national health registries in Denmark and Finland, we identified all children diagnosed with Prader-Willi syndrome (n = 143), Silver-Russell syndrome (n = 69), Beckwith-Wiedemann syndrome (n = 105) and Angelman syndrome (n = 72) born between 1994/1990 and 2014, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a total of 388 children diagnosed with imprinting disorders; 16 of these were conceived after ART. The overall AOR for the four imprinting disorders in ART children compared with NC children was 1.35 [95% CI: 0.80-2.29], but since eight ART children were diagnosed with Beckwith-Wiedemann syndrome, the AOR for this specific imprinting disorder was 2.84 [95% CI: 1.34-6.01]. The absolute risk of Beckwith-Wiedemann syndrome in children conceived after ART was still low: 10.7 out of 100 000 newborns. The risks of Prader-Willi syndrome, Silver-Russell syndrome and Angelman syndrome were not increased in children conceived after ART. LIMITATIONS, REASONS FOR CAUTION: Imprinting disorders are rare events and our results are based on few ART children with imprinting disorders. The aetiology is complex and only partly clarified, and the clinical diagnoses are challenged by a broad phenotypic spectrum. WIDER IMPLICATIONS OF THE FINDINGS: In the existing studies, results on the risk of imprinting disorders in children conceived after ART are ambiguous. This study adds that the risk of imprinting disorders in ART children is very small and perhaps restricted to Beckwith-Wiedemann syndrome.
|
|
| 5. |
- Klemetti, R., et al.
(författare)
-
Puberty disorders among ART-conceived singletons: a Nordic register study from the CoNARTaS group
- 2022
-
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:10, s. 2402-2411
-
Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Do ART-conceived children have an increased risk for puberty disorders? SUMMARY ANSWER Both ART-conceived boys and girls had a higher risk of puberty disorders; early puberty was more common among girls and late puberty among boys. WHAT IS KNOWN ALREADY Some physiological differences in growth and metabolism have been reported for ART-conceived children compared to non-ART-conceived children. Knowledge on pubertal development and disorders in ART-conceived children is limited. STUDY DESIGN, SIZE, DURATION A register-based cohort study was carried out including data from 1985 to 2015. The Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) study population consists of all live and stillborn children, as well as their mothers, registered in the Medical Birth Registers during the study period in Denmark, Sweden, Finland and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 122 321 ART-conceived singletons and 6 576 410 non-ART singletons born in Denmark (1994-2014), Finland (1990-2014), Norway (2002-2015) and Sweden (1985-2015) were included. Puberty disorders were defined using International Classification of Diseases and Related Health Problems (ICD)-9/ICD-10 codes and classified in the following groups: late puberty (6268/E30.0), early puberty (2591 and 2958/E30.1 and E30.8) and unspecified disorders (V212 and V579/E30.9 and Z00.3 as well as Z51.80 for Finland). The results in Cox regression were adjusted for maternal age, parity, smoking, gestational diabetes, chronic hypertension, hypertensive disorders during pregnancy and country, and further for either gestational age, birthweight, small for gestational age or large for gestational age. MAIN RESULTS AND THE ROLE OF CHANCE There were 37 869 children with diagnoses related to puberty disorders, and 603 of them were born after ART. ART-conceived children had higher risks for early (adjusted hazard ratio (aHR) 1.45, 95% CI: 1.29-1.64) and late puberty (aHR 1.47, 95% CI: 1.21-1.77). Girls had more diagnoses related to early puberty (aHR 1.46, 95% CI: 1.29-1.66) and boys with late puberty (aHR 1.55, 95% CI: 1.24-1.95). LIMITATIONS, REASONS FOR CAUTION Using reported puberty disorders with ICD codes in health care registers might vary, which may affect the numbers of cases found in the registers. Register data may give an underestimation both among ART and non-ART-conceived children, especially among non-ART children, who may not be as carefully followed as ART-conceived children. Adjustment for causes and duration of infertility, mothers' own puberty characteristics and BMI, as well as children's BMI, was not possible because data were not available or data were missing for the early years. It was also not possible to compare ART to non-ART siblings or to study the pubertal disorders by cause of subfertility owing to a small number of discordant sibling pairs and a large proportion of missing data on cause of subfertility. WIDER IMPLICATIONS OF THE FINDINGS This large, register-based study suggests that ART-conceived children have a higher risk for puberty disorders. However, the mechanisms of infertility and pubertal onset are complex, and ART is a rapidly advancing field with various treatment options. Studying the pubertal disorders of ART-conceived offspring is a continuing challenge. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk (71450), the Central Norway Regional Health Authorities (46045000), the Nordic Federation of Obstetrics and Gynaecology (NF13041, NF15058, NF16026 and NF17043), the Interreg oresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project), the Research Council of Norway's Centre of Excellence funding scheme (262700), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and FLUX Consortium 'Family Formation in Flux-Causes, Consequences and Possible Futures', funded by the Strategic Research Council, Academy of Finland (DEMOGRAPHY 345130). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest to disclose.
|
|
| 6. |
- Magnus, M. C., et al.
(författare)
-
Maternal Risk of Cardiovascular Disease After Use of Assisted Reproductive Technologies
- 2023
-
Ingår i: Jama Cardiology. - 2380-6583. ; 8:109, s. 837-845
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Studies examining the associations of different combinations of intensity-specific aerobic and muscle strengthening activity (MSA) with all-cause and cause-specific mortality are scarce; the few available estimates are disparate.OBJECTIVE To examine the prospective associations of different combinations of moderate aerobic physical activity (MPA), vigorous aerobic physical activity (VPA), and MSA with all-cause, cardiovascular (CVD), and cancer mortality.DESIGN, SETTING, AND PARTICIPANTS This nationwide prospective cohort study used data from the US National Health Interview Survey. A total of 500705 eligible US adults were included in the study and followed up during a median of 10.0 years (5.6 million person-years) from 1997 to 2018. Data were analyzed from September 1 to September 30, 2022. EXPOSURES Self-reported cumulative bouts (75 weekly minutes) of MPA and VPA with recommended MSA guidelines (yes or no) to obtain 48 mutually exclusive exposure categories.MAIN OUTCOMES AND MEASURES All-cause, CVD, and cancer mortality. Participants were linked to the National Death Index through December 31, 2019.RESULTS Overall, 500 705 participants (mean [SD] age, 46.4 [17.3] years; 210 803 [58%] female; 277 504 [77%] White) were included in the study. Compared with the reference group (doing no MPA or VPA and less than recommended MSA), the category associated with the lowest hazard ratio (HR) for all-cause mortality was more than 0 to 75 minutes of MPA combined with more than 150 minutes of VPA and 2 or more MSA sessions per week (HR, 0.50; 95% CI, 0.42-0.59). The optimal combinations for CVD and cancer mortality risk reduction were more than 150 to 225 minutes of MPA, more than 0 to 75 minutes of VPA, and 2 or more MSA sessions per week (HR, 0.30; 95% CI, 0.15-0.57), and more than 300 minutes of MPA, more than 0 to 75 minutes of VPA, and 2 or more MSA sessions per week (HR, 0.44; 95% CI, 0.23-0.82), respectively. Adjusted mortality rates represented an approximately 50% lower mortality rate for all-cause and cancer mortality and an approximately 3-fold lower mortality rate for CVD mortality. CONCLUSIONS AND RELEVANCE This cohort study demonstrated that balanced levels of MPA, VPA, and MSA combined may be associated with optimal reductions of mortality risk. Higher-than-recommended levels of MPA and VPA may further lower the risk of cancer and all-cause mortality, respectively.
|
|
| 7. |
- Petersen, S. H., et al.
(författare)
-
Time trends in placenta-mediated pregnancy complications after assisted reproductive technology in the Nordic countries
- 2020
-
Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 223:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of assisted reproductive technology is increasing worldwide and conception after assisted reproduction currently comprises 3%–6% of birth cohorts in the Nordic countries. The risk of placenta-mediated pregnancy complications is greater after assisted reproductive technology compared with spontaneously conceived pregnancies. Whether the excess risk of placenta-mediated pregnancy complications in pregnancies following assisted reproduction has changed over time, is unknown. Objectives: To investigate whether time trends in risk of pregnancy complications (hypertensive disorders in pregnancy, placental abruption and placenta previa) differ for pregnancies after assisted reproductive technology compared with spontaneously conceived pregnancies during 3 decades of assisted reproduction treatment in the Nordic countries. Study Design: In a population-based cohort study, with data from national health registries in Denmark (1994–2014), Finland (1990–2014), Norway (1988–2015) and Sweden (1988–2015), we included 6,830,578 pregnancies resulting in delivery. Among these, 146,998 (2.2%) were pregnancies after assisted reproduction (125,708 singleton pregnancies, 20,668 twin pregnancies and 622 of higher order plurality) and 6,683,132 (97.8%) pregnancies were conceived spontaneously (6,595,185 singleton pregnancies, 87,106 twin pregnancies and 1,289 of higher order plurality). We used logistic regression with post-estimation to estimate absolute risks and risk differences for each complication. We repeated analyses for singleton and twin pregnancies, separately. In subsamples with available information, we also adjusted for maternal body mass index, smoking during pregnancy, previous cesarean delivery, culture duration, and cryopreservation. Results: The risk of each placental complication was consistently greater in pregnancies following assisted reproductive technology compared with spontaneously conceived pregnancies across the study period, except for hypertensive disorders in twin pregnancies, where risks were similar. Risk of hypertensive disorders increased over time in twin pregnancies for both conception methods, but more strongly for pregnancies following assisted reproductive technology (risk difference, 1.73 percentage points per 5 years; 95% confidence interval, 1.35–2.11) than for spontaneously conceived twins (risk difference, 0.75 percentage points; 95% confidence interval, 0.61–0.89). No clear time trends were found for hypertensive disorders in singleton pregnancies. Risk of placental abruption decreased over time in all groups. Risk differences were –0.16 percentage points (95% confidence interval, –0.19 to –0.12) and –0.06 percentage points (95% confidence interval, –0.06 to –0.05) for pregnancies after assisted reproduction and spontaneously conceived pregnancies, respectively, for singletons and multiple pregnancies combined. Over time, the risk of placenta previa increased in pregnancies after assisted reproduction among both singletons (risk difference, 0.21 percentage points; 95% confidence interval, 0.14–0.27) and twins (risk difference, 0.30 percentage points; 95% confidence interval, 0.16–0.43), but remained stable in spontaneously conceived pregnancies. When adjusting for culture duration, the temporal increase in placenta previa became weaker in all groups of assisted reproductive technology pregnancies, whereas adjustment for cryopreservation moderately attenuated trends in assisted reproductive technology twin pregnancies. Conclusions: The risk of placenta-mediated pregnancy complications following assisted reproductive technology remains higher compared to spontaneously conceived pregnancies, despite declining rates of multiple pregnancies. For hypertensive disorders in pregnancy and placental abruption, pregnancies after assisted reproduction follow the same time trends as the background population, whereas for placenta previa, risk has increased over time in pregnancies after assisted reproductive technology. © 2020 Elsevier Inc.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Henningsen, A. K. A., et al.
(författare)
-
Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection: a Nordic study from the CoNARTaS group
- 2023
-
Ingår i: Fertility and Sterility. - 0015-0282 .- 1556-5653. ; 120:5, s. 1033-1041
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether the risk of major congenital malformations is higher in live-born singletons conceived with intracytoplasmic sperm injection (ICSI) compared with in vitro fertilization (IVF)?Design: Nordic register-based cohort study.Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers in Denmark, Norway and Sweden. Data were included from the year the first child conceived using ICSI was born: Sweden, 1992; Denmark, 1994; and Norway, 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden. Patient(s): All live-born singletons conceived using fresh ICSI (n = 32,484); fresh IVF (n = 47,178); without medical assistance (n = 4,804,844); and cryo-ICSI (n = 7,200) during the study period. Intervention(s): Different in vitro conception methods, and cryopreservation of embryos.Main Outcome Measure(s): Risk of major congenital malformations on the basis of International Classification of Diseases codes. The European Concerted Action on Congenital Anomalies and Twins was used to differentiate between major and minor malformations. Result(s): Among singletons conceived using fresh ICSI, 6.0% had a major malformation, compared with 5.3% of children conceived using fresh IVF; 4.2% of children conceived without medical assistance; and 4.9% of children conceived using cryoICSI; adjusted odds ratio (AOR) 1.07 (95% confidence interval [CI] 1.01-1.14) in ICSI vs. IVF; and AOR 1.28 (95% CI, 1.23- 1.35) in ICSI vs. no medical assistance; and AOR 1.11 (95% CI, 0.99-1.26) in ICSI fresh vs. cryo-ICSI. When malformations were grouped by different organ systems, children conceived using ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived using IVF, but there were very few cases in each group. When categorizing children conceived using ICSI according to treatment indication (male factor infertility only vs. other indications), we found a higher risk of hypospadias when ICSI was performed because of male factor infertility only (AOR 1.85 [95% CI 1.03-332]). The indications for ICSI changed over time, as male factor infertility did not remain the primary indication for ICSI throughout the study period.Conclusion(s): In this large cohort study, we found the risk of major malformations in live-born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing the assisted reproductive technology method for couples without male factor infertility. (Fertil Sterile 2023;120:1033-41. (c) 2023 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.
|
|
